Production of esters of alpha-hydroxy carboxylic acids



yli'c acids. a

fatented Nov. 10, 1931 UNITED STATES PATENT o-Fi-"ica WILHELM MICHAEL ANDWALTEB aas, of lnUnwiGSH-AEEN-ON-THE-RHI E, GER- MANY, ASSIGNORS TO I. e. FARBENIND'USTRIE AKTIENGESELLSCHAFT', or FRANK- FORT-ON-THE-MAIN, GERMANY, A ooRroRATIoNoF GERMANY rRoD o'rIon or Es'rnRs or a-H-YDROXY CARZBOXYLIG ACIDS V T NoDrawing; Application filedJune 26,-1929,"Seria1'No. 373,935,- and in Germany July 5, 1928.'

The present invention relates to the roduction of esters of alpha-hydroxy car ox- In the application for U. S. A. patent Serial N 0. 300,37 9 filed August 17 1928 we have described a process forthe production a of alpha-hydroxy carboxylic acids from their nitriles by which the saponification of the nitriles is carried out with acids in the presence of an inert solvent which is capable of dissolving the reacting substances and the reaction productswith the exception of the resulting ammonium salt, an amount, of

water sufficient for the sap'oniflcation being added, or by preparing already the nitriles from organic carbonyl compounds, i. e, from aldehydes, or ketones, and hydrocyanic acid in the presence of a solvent of'the aforesaid nature and thensaponifying the nitriles in the aforesaidmannen We have now found that esters of the alpha-hydroxy carboxylic acidsare obtained with particular advantage by carrying out the preparation of the nitriles and the conversion of the same into esters preferably in one operation in an inert solvent which is capable of dissolving the reacting. components and the reaction products with the exception of the resulting ammonium salt. Suitable solvents for this purpose are for example dioxane, tetrachlorethane, ethyl ether, chloroform, hexahydrobenzene and the,

like and also mixtures of these substances.

The process in accordance with the present invention may be carried out for example as follows :-Liquid or gaseous hydrocyanic acid is introduced at a moderately elevated temperature into a mixture consisting of the inert solvent, the required aldehyde or ketone, the alcohol required for esterifying and a small quantity of alkali as a catalyst, and in this manner the corresponding alphahydroxy carboxylic acid nitrile is obtained. Gaseous hydrochloric acid is then passed in and the theoretical quantity of water necessary for the formation of the ester is added. The nitrile is thus converted directly into the ester of the alpha-hydroxy carboxylic acid corresponding thereto, with the omission of the intermediate formation of the free acid. The ester, which is obtained in an excellent yield, can be easily isolated, for example by distillation. The alcohol necessary for the 'esterification canif desired be added after the formation of the nitrile instead of beforehand. Similarly the hydrotZYLIllC acld can be added to the mixture of nert solvent and alcohol and the aldehyde esters of the correspondingv hydroxy carboxylic acids, which esters can be prepared otherwise only with difficulty, V The following examples will further illustrate the'nature of the said invention but the invention is notrestricted to these examples.

Example] 27 kilograms of liquid or, gaseous hydrocyanic acid are gradually introduced into a mlxture-of 100 litres of dioxan e, 67 litres of 90 per cent acetaldehyde and 12 litres of decmormal caustic soda solution in a reaction vessel fitted with anice-cooled reflux condenser. The reaction mixture becomes heated. to from 70 to 80 centigradewith the formation of lactic acid nitrile and is kept at this temperature until the end ofthe reaction.

120 kilograms of cyclohexanol are then added and gaseous hydrochloric acid is passed in, preferably while cooling. The water necessary forthe formation of the ester is already present 1n the caustic soda. solution and in the acetaldehyde. The reaction mixture is heated-to boiling and esterification occurs. The ammonium chloride which separates out is filtered off and washed with a little dioxane. 'Ifthe esterification should not be complete more hydrochloric acid ispassed into the filtrate while heating. the same to boiling.

Anyhydrochloric acid present in the mixture can be removed by passing in a current of dry gaseous ammonia. Any further ammonium chloride produced is then filtered ofi and the filtrate distilled, and cyclohexanol lactate, boiling atffrom 95 to 110centigrade at 7 L 7 salt, adding,

millimetres (mercury gauge) is obtained. The yield amounts to about 165 kilograms which is equivalent to 96 per cent of the theoretical yield.

Example 2 d In a manner analogous to that described in Example 1, oz. -dihydroxy alerie acid chlor ethyl ester is obtained from aldol, hydrocyanic acid and ethylene chlorhydrin in the presence of chloroform as the inert solvent. The ester boils between and centigrade at 10 millimetres (mercury gauge) and about 84; per cent of the theoretical yield is obtained.

Example 3 90 per cent of the theoretical yield is obtained.

lVe claim: 1. The process for the production of esters of alpha-hydroxy carboxylic acids which comprises acting with hydrocya'nic acid on an organic carbonyl compound n the presence of an inert organic solvent capable of dissolvlng the reacting components and the reaction products,but not the resulting ammonium at any stage, an alcohol in a quantity required for the format-ion of the desired ester and introducing the quantity of water required fortheesterification and a strong inorganic acid.

" 2; The process for the production of esters of alpha-hydroxy carboxylic acids which comprises acting with hydrocyanic acid onan organic carbonyl compound in the presence of an inert organic solvent capable of dissolving the reacting components and the reaction products, but not the resulting ammon um salt, adding an alcohol in a quantity. required for the tormatlon of the desired ester and in-' troducing the quantity of water required for the esterification and a strong inorganic acid.

3. The process for the production of esters of alpha-hydroxy carboxylic acids which comprises acting with hydrocyanic acid on an organic carbonyl compound in the presence of an inertorganic solvent capable of dissolving the reacting components and the reactlon organic carbonyl compound in the presence of an inert organic solvent capable of dissolving the reacting components and the reaction products, but not the resulting ammonium salt, and of a small quantity ofa-n alkaline agent, adding an alcohol in a quantity re .quired for the formation of the desired ester and introducing the quantity of water requiredifor the esteri-fication and a strong inorganic acid. l

' '5. The process'for the production of esters of alpha-hydroxy carboxylic acids which comprises acting with hydrocyanic acid on an organic carbonyl compound in the presenc of an inert organic solvent capable of dissolving the reacting ;.componcnts and the r actio p od ts, but not the resulting ammonium salt, of a small quantity of an alkaline agent, and of an alcohol in .a quantity required for the formation of the desired ester, a d 111- troducing the quantity of water requiredior the esterification and a strong inorganic acid.

6. The process for the production of esters of alpha-hydroxy carboxylic acids which comprises acting with hydrocyanic acid on anorganic carbonyl compound in the P QSGILGB 0f dioxane, adding, at any stage, an alcohol in a quantity required for the formation of the desired ester and introducing the quantity. of water. required for the esterificati n and a" strong inorganic acid. 7 l

7. The process for he production of esters of alphashydroxy carhoxylic acids whi h comprises acting with hydrocy nic a id on an organic carbonyl compound the presence of dioxane, ofa small quantity of an alkaline agent, and of an alcohol in a qua ity required for the formation'of the desired e te and introducingt hc quantity ofwa'ter required for the esterification and a strong inorganic acid. a r

V In testimony whereof we have hereunto set our hands.

ILHELM MICHAEL. WALTER HAAG.

products, but not the resulting ammonium V J salt, and of an alcohol in a quantity required for the formation of the desired ester and introducing the quantity of water required for the esterification and a stronginorganic acid.

e. The process for the production of esters of alpha-hydroxy carboxylic acids which comprises acting with hydrocyanic acid on an ice 

